Fungal-Mediated Biotransformation of the Plant Growth Regulator Forchlorfenuron by .

The synthetic cytokinin forchlorfenuron (FCF), while seemingly presenting relatively low toxicity for mammalian organisms, has been the subject of renewed scrutiny in the past few years due to its increasing use in fruit crops and potential for bioaccumulation. Despite many toxicological properties of FCF being known, little research has been conducted on the toxicological effects of its secondary metabolites. Given this critical gap in the existing literature, understanding the formation of relevant FCF secondary metabolites and their association with mammalian metabolism is essential.

Development of Potential Multi-Target Inhibitors for Human Cholinesterases and Beta-Secretase 1: A Computational Approach.

Alzheimer's disease causes chronic neurodegeneration and is the leading cause of dementia in the world. The causes of this disease are not fully understood but seem to involve two essential cerebral pathways: cholinergic and amyloid. The simultaneous inhibition of AChE, BuChE, and BACE-1, essential enzymes involved in those pathways, is a promising therapeutic approach to treat the symptoms and, hopefully, also halt the disease progression.

Identification of Potential Multitarget Compounds against Alzheimer's Disease through Pharmacophore-Based Virtual Screening.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive loss of cognitive functions, and it is the most prevalent type of dementia worldwide, accounting for 60 to 70% of cases. The pathogenesis of AD seems to involve three main factors: deficiency in cholinergic transmission, formation of extracellular deposits of β-amyloid peptide, and accumulation of deposits of a phosphorylated form of the TAU protein. The currently available drugs are prescribed for symptomatic treatment and present adverse effects such as hepatotoxicity, hypertension, and weight loss.

Molecular Multi-Target Approach for Human Acetylcholinesterase, Butyrylcholinesterase and -Secretase 1: Next Generation for Alzheimer's Disease Treatment.

Alzheimer's Disease (AD) is a neurodegenerative condition characterized by progressive memory loss and other affected cognitive functions. Pharmacological therapy of AD relies on inhibitors of the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), offering only a palliative effect and being incapable of stopping or reversing the neurodegenerative process. However, recent studies have shown that inhibiting the enzyme β-secretase 1 (BACE-1) may be able to stop neurodegeneration, making it a promising target.

Identification of potential human beta-secretase 1 inhibitors by hierarchical virtual screening and molecular dynamics.

Alzheimer's disease (AD) is a neurodegenerative pathology responsible for 70% of dementia cases worldwide. Despite its relevance, the few drugs available for the treatment of this disease offer only symptomatic relief, with limited efficacy and serious adverse effects. The most accepted hypothesis about the pathogenesis involves the aggregation and deposition of β-amyloid peptides, mainly in the cerebral cortex and hippocampus, through the catalytic action of beta-secretase 1 (BACE-1), making this enzyme a promising target for the development of new drugs.

Evaluation of Docking Machine Learning and Molecular Dynamics Methodologies for DNA-Ligand Systems.

DNA is a molecular target for the treatment of several diseases, including cancer, but there are few docking methodologies exploring the interactions between nucleic acids with DNA intercalating agents. Different docking methodologies, such as AutoDock Vina, DOCK 6, and Consensus, implemented into Molecular Architect (MolAr), were evaluated for their ability to analyze those interactions, considering visual inspection, redocking, and ROC curve. Ligands were refined by Parametric Method 7 (PM7), and ligands and decoys were docked into the minor DNA groove (PDB code: 1VZK).

Endoscopic ultrasound hemostasis techniques.

Since its development, endoscopic ultrasound (EUS) has evolved from a simple diagnostic technique to an important therapeutic tool for interventional endoscopy. EUS analysis provides real-time imaging of most major thoracic and abdominal vessels, and the possibility to use needle puncture with a curved linear array echoendoscope as a vascular intervention. In this review, we describe the endoscopic ultrasound approach to vascular therapy outside of the gastrointestinal wall.

Click chemistry decoration of amino sterols as promising strategy to developed new leishmanicidal drugs.

A series of 1,2,3-triazolylsterols was prepared from pregnenolone through reductive amination and copper(I)-catalyzed azide-alkyne cycloaddition (click chemistry). The newly generated stereocenter of the key propargylamino intermediate provided a mixture of diastereomers which were separated chromatographically, and the configuration of the R isomer was determined by X-ray crystallography. Ten triazolyl sterols were prepared, and the products and intermediates were screened in vitro against different parasites, with some compounds presenting IC50 values in the low micromolar range against Leishmania donovani.

Design, synthesis, and docking studies of novel benzimidazoles for the treatment of metabolic syndrome.

In addition to lowering blood pressure, telmisartan, an angiotensin (AT(1)) receptor blocker, has recently been shown to exert pleiotropic effects as a partial agonist of nuclear peroxisome proliferator-activated receptor gamma (PPAR gamma). On the basis of these findings and docking pose similarity between telmisartan and rosiglitazone in PPAR gamma active site, two classes of benzimidazole derivatives were designed and synthesized as dual PPAR gamma agonist/angiotensin II antagonists for the possible treatment of metabolic syndrome. Compound 4, a bisbenzimidazole derivative showed the best affinity for the AT(1) receptor with a K(i) = 13.

1,3-Diaxially substituted trans-decalins: potential nonsteroidal human progesterone receptor inhibitors.

On the basis of molecular modeling and QSAR analysis of the known human progesterone receptor (hPR) inhibitor Mifepristone (RU-486) and other hPR ligands, a new class of potential nonsteroidal hPR inhibitors was designed. The parent racemic compound 1 was synthesized through an efficient 13-step synthetic pathway. The key constructive steps are a stereoselective epoxide ring opening and the reductive Heck cyclization to form the main framework of (+/-)-1.

7β-Hydroxy-artemisinin.

CRYSTALS OF THE TITLE COMPOUND [SYSTEMATIC NAME: (3R,6R,7S,8aR,9R,12aR)-7-hydr-oxy-3,6,9-trimethyl-octa-hydro-3,12-ep-oxy[1,2]dioxepino[4,3-i]isochromen-10(3H)-one], C(15)H(22)O(6), were obtained from microbial transformation of artemisinin by a culture of Cunninghamella elegans. The stereochemistry of the compound is consistent with the spectroscopic findings in previously published works. A weak O-H⋯O hydrogen bond occurs in the crystal structure, together with intermolecular C-H⋯O hydrogen bonds.

Total synthesis and absolute configuration of laurenditerpenol: a hypoxia inducible factor-1 activation inhibitor.

The absolute stereo structure of the natural product laurenditerpenol (1S, 6R, 7S, 10R, 11R, 14S, 15R) has been accomplished from eight plausible stereoisomers by its first asymmetric total synthesis in a highly convergent and flexible synthetic pathway. Six stereoisomers of laurenditerpenol were synthesized and evaluated for their biological activity.